SciCombinator

Discover the most talked about and latest scientific content & concepts.

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Cyclic dinucleotides (CDNs) have central roles in bacterial homeostasis and virulence by acting as nucleotide second messengers. Bacterial CDNs also elicit immune responses during infection when they are detected by pattern-recognition receptors in animal cells. Here we perform a systematic biochemical screen for bacterial signalling nucleotides and discover a large family of cGAS/DncV-like nucleotidyltransferases (CD-NTases) that use both purine and pyrimidine nucleotides to synthesize a diverse range of CDNs. A series of crystal structures establish CD-NTases as a structurally conserved family and reveal key contacts in the enzyme active-site lid that direct purine or pyrimidine selection. CD-NTase products are not restricted to CDNs and also include an unexpected class of cyclic trinucleotide compounds. Biochemical and cellular analyses of CD-NTase signalling nucleotides demonstrate that these cyclic di- and trinucleotides activate distinct host receptors and thus may modulate the interaction of both pathogens and commensal microbiota with their animal and plant hosts.

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Photocatalytic hydrogen evolution from water has received enormous attention due to its ability to address a number of global environmental and energy-related issues. Here, we synthesize 2D/2D Ti3C2/g-C3N4 composites by electrostatic self-assembly technique and demonstrate their use as photocatalysts for hydrogen evolution under visible light irradiation. The optimized Ti3C2/g-C3N4 composite exhibited a 10 times higher photocatalytic hydrogen evolution performance (72.3 μmol h-1 gcat-1) than that of pristine g-C3N4 (7.1 μmol h-1 gcat-1). Such enhanced photocatalytic performance was due to the formation of 2D/2D heterojunctions in the Ti3C2/g-C3N4 composites. The intimate contact between the monolayer Ti3C2 and g-C3N4 nanosheets promotes the separation of photogenerated charge carriers at the Ti3C2/g-C3N4 interface. Furthermore, the ultrahigh conductivity of Ti3C2 and the Schottky junction formed between g-C3N4/MXene interfaces facilitate the photoinduced electron transfer and suppress the recombination with photogenerated holes. This work demonstrates that the 2D/2D Ti3C2/g-C3N4 composites are promising photocatalysts thanks to the ultrathin MXenes as efficient co-catalysts for photocatalytic hydrogen production.

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The epidemiology and implant specific risk for BIA-ALCL has been previously reported for Australia and New Zealand. We now present updated data and risk assessment since our last report.

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Eosinophilic esophagitis (EoE) is a chronic, inflammatory condition of the esophagus. Prevalence of EoE is on the rise and, owing to its associated extragastrointestinal manifestations and comorbidities, otolaryngologists are increasingly encountering this condition in their practice.

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The present study aimed to investigate and identify the association between the intake of allium vegetables and colorectal cancer (CRC) in population.

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Regio and stereoselective activation of sp3 CH bonds remain one of the major advantages of biocatalysis over traditional chemocatalytic methods. Herein, we describe the oxy-functionalization of halimane diterpenoid 1 by whole cells of three filamentous fungi, aiming to obtain derivatives with desirable biological properties. After incubating 1 with Fusarium oxysporum, Myrothecium verrucaria, and Rhinocladiella similis at different concentrations and incubation times, four known (3, 5, 6, and 7) and three new (2, 4, and 8) halimane derivatives were obtained and characterized. F. oxysporum catalyzed the hydroxylation of positions C-2 (2) and C-7 (4), while R. similis simultaneously mediated the 2-oxo-functionalization and the hydration of 13,14-(CC)double bond belonging to an α,β-unsaturated carbonyl system (8). Compounds 1-7 were non-cytotoxic against HCT-116 and MCF-7 cancer cell lines at tested concentrations. However, substrate 1 displayed moderate reduction ability against biofilm produced by Staphylococcus epidermidis ATCC35984 (84% at 1.6 mM), and this effect was retained to some extent by derivatives 4 and 7. These results emphasize the prominent potential of filamentous fungi associated with the microbiota of medicinal plants as versatile catalysts for singularly useful reactions through their complex enzymatic machinery, as well as the high susceptibility of halimane-diterpenoid substrates.

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Since lacosamide was approved as an adjuvant agent for the treatment of medically refractory focal epilepsy over ten years ago, it is becoming more widely used for the treatment of idiopathic (genetic) generalized epilepsies. Several studies have demonstrated efficacy in reducing primary generalized tonic-clonic seizures (GTCS), but efficacy is less well-characterized for myoclonic and absence seizures. A 29-year-old man with juvenile myoclonic epilepsy and medically refractory GTCS on a combination of levetiracetam and topiramate was started on lacosamide adjunctive therapy with the plan to replace topiramate. While his GTCS became controlled, he was witnessed to have confusional episodes, with waxing and waning responsiveness, lasting a few days, several times a month. After eight months of adjunctive lacosamide therapy, he was admitted to the epilepsy monitoring unit, where paroxysms of generalized spike-and-wave complexes, lasting for 30-90 minutes, were recorded, interrupted only by sleep. During these periods, he demonstrated psychomotor slowing and disorientation on examination. The absence status was successfully broken by lorazepam, and lacosamide was discontinued. The patient had no further confusional episodes at the most recent follow-up visit, four months after discharge.

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To increase cancer immunotherapy success, PD-1 blockade must be combined with rationally selected treatments. Here, we examined, in a poorly immunogenic mouse breast cancer model, the potential of antibody-based immunomodulation and conventional anticancer treatments to collaborate with anti-PD-1 treatment. One requirement to improve anti-PD-1-mediated tumor control was to promote tumor-specific cytotoxic T-cell (CTL) priming, which was achieved by stimulating the CD137 costimulatory receptor. A second requirement was to overrule PD-1-unrelated mechanisms of CTL suppression in the tumor micro-environment (TME). This was achieved by radiotherapy (RT) and cisplatin treatment. In the context of CD137/PD-1-targeting immunotherapy, RT allowed for tumor elimination by altering the TME, rather than intrinsic CTL functionality. Combining this radioimmunotherapy (RIT) regimen with low-dose cisplatin improved CTL-dependent regression of a contralateral tumor outside the radiation field. Thus, systemic tumor control may be achieved by combining immunotherapy protocols that promote T-cell priming with (chemo)radiation protocols that permit CTL activity in both the irradiated tumor and (occult) metastases.

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Human papilloma virus (HPV)-related squamous cell carcinoma (SCC) is biologically unique and has a better prognosis than conventional SCC of the head and neck. p16 immunohistochemistry emerged as a valuable surrogate marker for HPV in oropharyngeal SCC. The criteria for a positive p16 result in tissue specimens are well established. However, there is no consensus regarding interpreting p16 staining in cell blocks and other cytology specimens. This review discusses the current evidence on p16 testing in cytology specimens and also highlights other methods for HPV testing, including DNA and RNA in situ hybridization, as well as other molecular HPV tests.

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This short review focuses on pulmonary injury in breath-hold (BH) divers. When practicing their extreme leisure sport, they are exposed to increased pressure on pulmonary gas volumes, hypoxia, and increased partial gas pressures. Increasing ambient pressures do present a serious problem to BH deep divers, because the semi-rigid thorax prevents the deformation required by the Boyle-Mariotte law. As a result, a negative-pressure barotrauma (lung squeeze) with acute hemoptysis is not uncommon. Respiratory maneuvers such as glossopharyngeal insufflation (GI) and glossopharyngeal exsufflation (GE) are practiced to prevent lung squeeze and to permit equalizing the paranasal sinuses and the middle ear. GI not only impairs venous return, thereby provoking hypotension and even fainting, but also produces intrathoracic pressures likely to induce pulmonary barotrauma that is speculated to induce long-term injury. GE, in turn, further increases the already negative intrapulmonary pressure, thereby favoring alveolar collapse (atelectasis). Finally, hypoxia seemingly not only induces brain injury but initiates the opening of intrapulmonary shunts. These pathways are large enough to permit transpulmonary passage of venous N2 bubbles, making stroke-like phenomena in deep BH divers possible.